Hypertension Editors’ Picks

Abstract

HomeHypertensionVol. 63, No. 5Hypertension Editors’ Picks Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHypertension Editors’ PicksPregnancy, Hypertension, and Preeclampsia The Editors The Editors Search for more papers by this author Originally published10 Mar 2014https://doi.org/10.1161/HYPERTENSIONAHA.114.03061Hypertension. 2014;63:e93–e109Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2014: Previous Version 1 The following articles are being highlighted as part of Hypertension’s Editors’ Picks Series. During the last decade, there has been a surge in the interest in identifying and characterizing new pathways that lead to new onset hypertension during pregnancy. Novel animal models have been reported that should aid in the development of targeted therapies for preeclampsia. Several innovative biomarkers have been identified in humans and tested for use in prediction and diagnosis of preeclampsia and its complications. Hypertensive complications of pregnancy have also emerged as major risk factors for hypertension and cardiovascular disease in the mother and the offspring. We have collated for our readers all 45 full length basic and clinical articles on pregnancy and preeclampsia published in our Journal between January 2013 and January 2014. It is quite obvious from the articles listed that Hypertension, an American Heart Association Journal, has become an important home for the publication of high quality studies on pregnancy and preeclampsia.Matrix Metalloproteinase Enhances Big-Endothelin-1 Constriction in Mesenteric Vessels of Pregnant Rats With Reduced Uterine Blood Flow1AbstractPreeclampsia is a leading cause of maternal and fetal morbidity/mortality; however, the pathophysiological mechanisms are poorly understood. Vascular endothelial dysfunction in preeclampsia has been partially attributed to changes in endothelin-1 (ET-1). Several enzymes, including matrix metalloproteinases (MMPs, particularly MMP-2), cleave the inactive precursor bigET-1 (bET-1) to active ET-1. Notably, expression levels of MMP-2 have been shown to be increased in women who subsequently develop preeclampsia. We hypothesized that increased MMP-2 expression leads to increased bET-1 conversion, thus increasing vasoconstriction in preeclampsia. A reduced uteroplacental perfusion pressure (RUPP) model of preeclampsia in the rat was used to assess mesenteric artery vascular function. Responses to bET-1 (3–310 nmol/L) and ET-1 (1–200 nmol/L) were studied in the presence or absence of enzyme inhibitors known to cleave bET-1. Vascular contractility in response to bET-1 was greater in RUPP than Sham (P<0.0001), while neither responses to ET-1 nor maximal contractility to high potassium salt solution (KPSS, 123.70 mmol/L) were different. MMP inhibition with GM6001 (30 μmol/L) significantly decreased responses to bET-1 in RUPP (P<0.0001) but not Sham-operated rats. Interestingly, combined treatment with GM6001 and L-NAME (100 μmol/L) revealed a nitric oxide modulation of MMPs that was reduced in RUPP. In summary, we found increased vascular contractility to bET-1 in the RUPP model of preeclampsia that was likely attributable to upstream enzymatic pathways. These data are consistent with a greater contribution of MMP to cleavage of bET-1 to ET-1 ex vivo in RUPP, suggesting that this enzyme may be partially responsible for increased bET-1 induced contractility.The Impact of Malaria in Pregnancy on Changes in Blood Pressure in Children During Their First Year of Life2AbstractWe established a maternal-birth cohort in Ibadan, Nigeria where malaria is hyperendemic to assess how intrauterine exposure to malaria affected infant blood pressure (BP) development. In a local maternity hospital, healthy pregnant women had regular blood films for malaria parasites from booking to delivery. Growth and BP were measured on 318 babies, all followed from birth to 3 and 12 months. Main outcomes were standardised measures of anthropometry and change in BP to 1 year. Babies exposed to maternal malaria were globally smaller at birth and boys remained smaller at 3 months and 1 year. Change in systolic BP (SBP) over the year was greater in boys than girls (20.9 vs 15.7mm Hg P=0.002) but greater in girls exposed to maternal malaria (18.7 vs 12.7, 1–11, mm Hg, P=0.02). 11% of boys (> twice expected) had a SBP >95th percentile (hypertensive, US criteria) of whom 68% had maternal malaria exposure. On regression analysis (β coefficients, mm Hg), gender (boys>girls, β=4.4, 1.1–7.7; P=0.01), maternal malaria exposure (3.64, 0.3–6.9, P=0.03) and weight change (2.4, 0.98 to 3.8/1 SDS; P=0.001) all independently increased SBP change to 1 year, while increase in length decreased SBP (-1.98, -3.6 to -0.40). In conclusion, malaria-exposed boys had excess ‘hypertension,’ exposed girls a greater increase in SBP. Intrauterine exposure to malaria had gender-dependent effects on BP, independent of infant growth. As infant-child-adult BP tracking is powerful, a malarial effect may contribute to the African burden of hypertension.Pravastatin Attenuates Hypertension, Oxidative Stress, and Angiogenic Imbalance in Rat Model of Placental Ischemia-Induced Hypertension3AbstractPreeclampsia is a pregnancy-specific condition characterized by an imbalance of circulating angiogenic factors and new-onset hypertension. Although current treatment options are limited, recent studies suggest pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin would restore angiogenic balance and reduce mean arterial pressure (MAP) in rats with reduced utero-placental perfusion pressure (RUPP)-induced hypertension. Pravastatin was administered i.p. (1 mg/kg/day) in RUPP (RUPP+P) and normal pregnant rats (NP+P) from day 14–19 of pregnancy. On day 19, MAP was measured via catheter, conceptus data was recorded and tissues collected. MAP was increased (P<0.05) in RUPP compared to NP dams and pravastatin ameliorated this difference. Pravastatin attenuated decreased fetal weight and plasma VEGF and the RUPP-induced increased sFlt-1 when compared to NP dams. Pravastatin treatment did not improve angiogenic potential in RUPP serum and decreased (P<0.05) endothelial tube formation in NP rats. RUPP rats presented with indices of oxidative stress such as increased placental catalase activity and plasma TBARS along with decreased plasma total antioxidant capacity compared to NP controls and pravastatin attenuated these effects. MAP, fetal weight, plasma VEGF, and plasma sFlt-1 were unchanged in NP+P compared to NP controls. The present data indicate that treatment with pravastatin attenuates oxidative stress and lowers MAP in placental ischemia-induced hypertension, but may have negative effects on circulating angiogenic potential during pregnancy. Further studies are needed to determine if there are long-term deleterious effects on maternal or fetal health following pravastatin treatment during pregnancy-induced hypertension or preeclampsia.Endothelin-1, Oxidative Stress, and Endogenous Angiotensin II: Mechanisms of Angiotensin II Type I Receptor Autoantibody-Enhanced Renal and Blood Pressure Response During Pregnancy4AbstractHypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (MAP) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index (RARI) in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared to control pregnant rats. In order to examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy we examined the role of endogenous ANGII in AT1-AA infused pregnant rats, Endothelin-1 and oxidative stress in AT1-AA+ANGII treated rats. Chronic ANGII increased MAP from 95 +/-2 in NP rats to 115 +/-2 mm Hg. Chronic AT1-AA increased MAP to 118+/-1 mm Hg in NP rats which further increased to 123+/-2 with AT1-AA+ANGII. Increasing ANGII from (10-11-10-8) decreased Af-Art diameter 15–20% but sharply decreased Af-Art diameter 60% in AT1-AA pretreated vessels. RARI increased from 0.67 in NP rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA + ANGII infused rats. AT1-AA-induced hypertension decreased with Enalapril but was not attenuated. Both tissue ET-1 and ROS increased with AT1-AA+ANGII compared to AT1-AA alone and blockade of either of these pathways had significant effects on MAP or RARI. These data support the hypothesis that AT1-AA, via activation of ET-1 and oxidative stress and interaction with endogenous ANGII, are important mechanisms whereby MAP and renal vascular responses are enhanced during preeclampsia.Urinary Excretion of c5b-9 in Severe Preeclampsia: Tipping the Balance of Complement Activation in Pregnancy5AbstractThe complement cascade is activated in normal pregnancy and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. Consequently, biomarkers of complement dysregulation may be useful for prediction or treatment of disease. Since renal damage with proteinuria is a characteristic pathological feature of preeclampsia we hypothesized that complement markers in urine, rather than plasma, could better reflect complement dysregulation in disease. To investigate this we performed a case-control study of pregnant women, enrolling 25 cases of severe preeclampsia, 25 chronic hypertensive controls and 25 healthy non-hypertensive controls matched by gestational age and parity. Subjects were recruited from the Brigham and Women’s Hospital from March 2012 through March 2013. Urine and blood samples were collected on the day of enrollment, with complement activation (C3a, C5a and C5b-9) measured by ELISA. Severe preeclampsia was associated with marked elevations in urinary C5b-9 [median ng/ml (IQ range) 4.3 (1.2–15.1)] relative to subjects with chronic hypertension Ύ (0-0)] and healthy controls Ύ (0-0)], P<0.0001. Urinary excretion of C5b-9 was detected in 96% of severe preeclamptics, 12% of chronic hypertensives and 8% of healthy controls. Cases were also notable for significantly greater urinary excretion of C3a and C5a. Plasma levels of C5a and C5b-9, but not C3a, were increased in severe preeclampsia compared to healthy controls; however, they did not distinguish preeclampsia from chronic hypertension, supporting our hypothesis that complement markers in urine rather than plasma better reflect complement dysregulation. Complement inhibition is an intriguing treatment option for patients with severe preeclampsia.Preeclampsia Is Associated With the Presence of Transcriptionally Active Placental Fragments in the Maternal Lung6AbstractPreeclampsia is associated with increased levels of the circulating anti-angiogenic factor sFlt-1 and with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can therefore contribute to the systemic manifestations of preeclampsia. In this study, we measured placental sFlt-1 mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic and control subjects. To confirm the placental origin of these aggregates in maternal lungs, immunohistochemistry for the placenta-specific marker hCG and Y-chromosome in situ hybridization were performed. Using human placental tissue, we found that syncytial knots are the principal site of expression of the anti-angiogenic factor sFlt-1. In addition, autopsy material obtained from women with preeclampsia (n=9), showed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these aggregates still contained the anti-angiogenic factor sFlt-1 following their entrapment in the maternal lungs. The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. Additionally, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.Preterm Birth and Future Maternal Blood Pressure, Inflammation, and Intimal-Medial Thickness: The CARDIA Study7AbstractPreterm birth (PTB, <37 weeks) may be a marker of endothelial dysfunction and a proinflammatory phenotype; both are risk factors for cardiovascular disease. We studied 916 women (46% black) with 1181 live births between enrollment in the Coronary Artery Risk Development in Young Adults study (age 18–30 years) and 20 years later. C-reactive protein was measured at years 7, 15, and 20. Interleukin-6 and carotid intima-media thickness, which incorporated the common carotid arteries, bifurcations, and internal carotid arteries, were measured at year 20. Blood pressure, lipids, anthropometrics, and pregnancy events were assessed at all visits. Change in risk factors and differences in inflammatory markers and intima-media thickness according to PTB were evaluated. Women with PTBs (n=226) had higher mean systolic blood pressures before pregnancy (106 versus 105 mm Hg, respectively; P=0.03). Systolic and diastolic blood pressure increased more rapidly over 20 years compared with women with term births (P<0.01 time interaction), even after removing women with self-reported hypertension in pregnancy. Women with PTB versus term births had similar mean intima-media thickness adjusted for age, body mass index, race, lifestyle, and cardiovascular risk factors. C-reactive protein and interleukin-6 did not differ according to PTB. Women with PTB, regardless of hypertension during pregnancy, had higher blood pressure after pregnancy compared with women with term births. In the United States, where rates of PTB are high and race disparities persist, PTB may identify women with higher blood pressure in the years after pregnancy.Testosterone Alters Maternal Vascular Adaptations: Role of the Endothelial NO System8AbstractSex steroid hormones estradiol and progesterone play an important role in vascular adaptations during pregnancy. However, little is known about the role of androgens. Plasma testosterone (T) levels are elevated in preeclampsia, mothers with polycystic ovary, and pregnant African American women, who have endothelial dysfunction and develop gestational hypertension. We tested whether increased T alters vascular adaptations during pregnancy and whether these alterations depend on endothelium-derived factors, such as prostacyclin, endothelium-derived hyperpolarizing factor, and NO. Pregnant Sprague Dawley rats were injected with vehicle (n=12) or T propionate [0.5 mg/Kg per day from gestation day 15–19; n=12] to increase plasma T levels 2-fold, similar to that observed in preeclampsia. Telemetric blood pressures and endothelium-dependent vascular reactivity were assessed with wire-myograph system. Phospho-endothelial NO synthase and total endothelial NO synthase were examined in mesenteric arteries. Mean arterial pressures were significantly higher starting from gestation day19 until delivery in T-treated dams. Endothelium-dependent relaxation responses to acetylcholine were significantly lower in mesenteric arteries of T-treated dams (pD2 [−log EC50]=7.05±0.06; Emax=89.4±1.89) compared with controls (pD2=7.38±0.04; Emax=99.9±0.97). Further assessment of endothelial factors showed NO-mediated relaxations were blunted in T-treated mesenteric arteries (Emax=42.26±5.95) compared with controls (Emax=76.49±5.06); however, prostacyclin- and endothelium-derived hyperpolarizing factor-mediated relaxations were unaffected. Relaxation to sodium nitroprusside was unaffected with T-treatment. Phosphorylations of endothelial NO synthase at Ser1177 were decreased and at Thr495 increased in T-treated mesenteric arteries without changes in total endothelial NO synthase levels. In conclusion, increased maternal T, at concentrations relevant to abnormal clinical conditions, cause hypertension associated with blunting of NO-mediated vasodilation.Administration of Interleukin-17 Soluble Receptor C Suppresses TH17 Cells, Oxidative Stress, and Hypertension in Response to Placental Ischemia During Pregnancy9AbstractPreeclampsia, new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). Chronic IL-17 increases blood pressure (MAP), autoantibodies (AT1-AA) and ROS during pregnancy. The objective of this study was to determine TH17 suppression via IL-17RC (recombinant receptor C) decreases pathophysiology associated with placental ischemia (RUPP). On gestation day 14, mini-osmotic pumps infusing 100 pg/day of IL-17RC were implanted into pregnant rats undergoing RUPP (Reduced Uterine Perfusion Pressure), gestation day18 carotid catheters were inserted, day 19 MAP was recorded, TH17 cells, oxidative stress and AT1-AA were measured and analyzed via one-way ANOVA. MAP increased from 101 ±2 mm Hg in normal pregnant, NP (n=19), to 120 ±1 mm Hg in RUPP (n=17),but decreased to 110±2 mm Hg in RUPP+IL-17RC rats (n=22). Pup weight decreased from 2.28 ± 0.2 g in NP to 1.96 ± 0.3 g in RUPP rats, but was significantly increased to 2..1 in RUPP+IL-17RC rats. TH17 cells were 1.77% in RUPP but decreased to 0.65% in RUPP+IL-17RC rats. Urinary isoprostanes normalized in RUPP +IL-17RC rats (52 pg/μg) compared to 89 pg/μg in RUPP controls. Placental ROS was 652 RLU in RUPP, but decreased to 337 RLU in RUPP+IL-17RC rats. AT1-AA was 17.27 ± 0.7 bpm in RUPP but decreased to 5.00 ± 0.5 bpm in RUPP+IL-17RC rats. With this study, we show that infusion of IL-17RC blunts TH17s, oxidative stress, AT1-AA, and hypertension in the RUPP model of preeclampsia indicating that TH17 cells may play an important role in disease pathophysiology.Podocyturia Predates Proteinuria and Clinical Features of Preeclampsia: Longitudinal Prospective Study10AbstractPodocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.Parental Smoking in Pregnancy and the Risks of Adult-Onset Hypertension11AbstractFetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33 086 participants of the Nurses’ Health Study II and the Nurses’ Mothers’ Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8575 (25.9%) mothers and 18 874 (57.0%) fathers smoked during pregnancy. During follow-up, 7825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥15 cigarettes/d during pregnancy were associated with increased risks of hypertension (rate ratio, 1.19; 95% CI, 1.09–1.29; and rate ratio, 1.18; 95% CI, 1.12–1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, whereas additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (rate ratio, 1.07; 95% CI, 0.98–1.16; and rate ratio, 1.06; 95% CI, 1.01–1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.Preeclampsia-Like Symptoms Induced in Mice by Fetoplacental Expression of STOX1 Are Reversed by Aspirin Treatment12AbstractPreeclampsia is a common human-specific pregnancy disorder defined by hypertension and proteinuria during gestation and responsible for maternal and fetal morbimortality. STOX1, encoding a transcription factor, was the first gene associated with preeclampsia as identified by positional cloning approaches. Its overexpression in choriocarcinoma cells mimics the transcriptional consequences of preeclampsia in the human placenta. Here, we created transgenic mouse strains overexpressing human STOX1. Wild-type female mice crossed with transgenic male mice reproduce accurately the symptoms of severe PE: gestational hypertension, proteinuria, and elevated plasma levels of soluble fms-like tyrosine kinase 1 and soluble endoglin. Placental and kidney histology were altered. Symptoms were prevented or alleviated by aspirin treatment. STOX1-overexpressing mice constitute a unique model for studying preeclampsia, allow testing therapeutic approaches, and assessing the long-term effects of the preeclamptic syndrome.Hypertensive Disorders of Pregnancy and Cardiometabolic Health in Adolescent Offspring13AbstractAn accumulating body of evidence suggests that offspring of mothers with preeclampsia have higher blood pressure during childhood and young adulthood compared with women without preeclampsia. However, the evidence with regard to offspring glucose metabolism and lipids is more scant. We examined whether maternal hypertensive disorders of pregnancy (preeclampsia and gestational hypertension) are associated with a range of cardiometabolic health measures in adolescent offspring. We included data for mother–offspring pairs from a United Kingdom prospective birth cohort (the Avon Longitudinal Study of Parents and Children). Repeat antenatal clinic measures of blood pressure and proteinuria (median 14 and 11, respectively) were used to ascertain maternal preeclampsia (n=53) and gestational hypertension (n=431). Offspring had blood pressure (n=4438), and fasting lipids, insulin, and glucose (n=2888) measured at a mean age of 17 years. There was no strong evidence of differences in fasting insulin, glucose, or lipid concentrations. Systolic and diastolic blood pressures were higher in offspring of mothers with gestational hypertension (mean difference, 2.06 mm Hg; 95% confidence interval, 1.28–2.84 and 1.11 mm Hg; 95% confidence interval, 0.54–1.69, respectively) and preeclampsia (1.12 mm Hg; 95% confidence interval, −0.89–3.12 and 1.71 mm Hg; 95% confidence interval, 0.23–3.17, respectively) compared with offspring of mothers without hypertensive disorders of pregnancy, adjusting for potential confounders (age, sex, maternal age at delivery, household social class, prepregnancy body mass index, parity, and smoking in pregnancy). Results suggest a specific association between maternal hypertensive disorders of pregnancy and offspring blood pressure that may be driven by genetics or familial nongenetic risk factors particular to blood pressure.MicroRNA-376c Impairs Transforming Growth Factor-Beta and Nodal Signaling to Promote Trophoblast Cell Proliferation and Invasion14AbstractPreeclampsia is a major disorder of pregnancy and a leading cause of maternal and perinatal morbidity and mortality. MicroRNAs are small noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we examined the expression of miR-376c and found that miR-376c levels were downregulated in both placental and plasma samples collected from preeclamptic patients, when compared with the normal pregnant women at the same gestational stage. Overexpression of miR-376c induced trophoblast cell proliferation, migration, and invasion in HTR8/SVneo cells and promoted placental explant outgrowth. In contrast, inhibition of endogenous miR-376c resulted in a decrease in trophoblast cell invasion and placental explant outgrowth. We identified activin receptor-like kinase 5 (ALK5), a type I receptor for transforming growth factor-β, and ALK7, a type I receptor for Nodal, as targets of miR-376c. Overexpression of miR-376c repressed transforming growth factor-β and Nodal functions, whereas overexpression of ALK5 and ALK7 reversed the effects of miR-376c. These results demonstrate that miR-376c inhibits both ALK5 and ALK7 expression to impair transforming growth factor-β/Nodal signaling, leading to increases in cell proliferation and invasion. An unbalanced Nodal/transforming growth factor-β and miR-376c expression may lead to the development of preeclampsia.Maternal Prepregnancy Body Mass Index and Their Children’s Blood Pressure and Resting Cardiac Autonomic Balance at Age 5 to 6 Years15AbstractAdverse intrauterine conditions can program hypertension. Because one of the underlying mechanisms is thought to be cardiac autonomic balance, we investigated the association between pre-pregnancy body mass index (BMI) and blood pressure and indicators of the autonomic balance in the child at age 5–6 years. Also investigated was whether these associations were mediated by standardized birth weight and child BMI. Pregnant women (n=3074) participating in the ABCD study completed a questionnaire at gestational week 14. At age 5–6 years, offspring’s sympathetic drive (pre-ejection period), parasympathetic drive (respiratory sinus arrhythmia) and heart rate were measured by electrocardiography and impedance cardiography at rest. Blood pressure was assessed simultaneously. After adjusting for possible maternal/offspring confounders, pre-pregnancy BMI was positively linearly associated with diastolic blood pressure (β:0.11 mm Hg, 95% confidence interval [CI], 0.05–0.17), systolic blood pressure (β:0.14 mm Hg, 95% CI, 0.07–0.21), but not with heart rate, sympathetic or parasympathetic drive. After adding birth weight and child BMI to the model, the independent effect size of pBMI on SBP (β:0.07 mm Hg, 95% CI, 0.00–0.14) and DBP (β:0.07 mm Hg, 95% CI, 0.01–0.13) decreased by about 50%. Birth weight did not mediate these relationships, but was independently and negatively associated with blood pressure. Child BMI was positively associated with blood pressure and partly mediated the association between pre-pregnancy BMI and blood pressure. In conclusion, higher pre-pregnancy BMI is associated with higher blood pressure in the child (aged 5–6 years) but does not seem to be due to early alterations in resting cardiac autonomic balance. Child BMI, but not birth weight, mediated the association between pre-pregnancy BMI and blood pressure.Cellular Fetal Microchimerism in Preeclampsia16AbstractPrevious studies have shown elevated concentrations of free fetal DNA and erythroblasts in maternal circulation in women with preeclampsia compared with those with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal microchimerism in maternal circulation in women with preeclampsia and healthy controls. We studied women with preeclampsia and compared them with women with healthy pregnancies at similar gestational age. To identify a targetable polymorphism unique to the fetus to quantify fetal microchimerism, participants and family members were genotyped for the human leukocyte antigen loci DRB1, DQA1, and DQB1, as well as several other polymorphisms. A panel of polymorphism-specific quantitative polymerase chain reaction assays was used to identify and quantify fetal microchimerism in maternal peripheral blood mononuclear cells.